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- Title
p75NTR-dependent modulation of cellular handling of reactive oxygen species.
- Authors
Zhiping Mi; Rogers, Danny A.; Mirnics, Zeljka Korade; Schor, Nina Felice
- Abstract
Our previous studies demonstrated that p75NTR confers protection against oxidative stress-induced apoptosis upon PC12 cells; however, the mechanisms responsible for this effect are not known. The present studies reveal decreased mitochondrion membrane potential and increased generation of reactive oxygen species (ROS) in p75NTR-deficient PC12 cells as well as diminution of ROS generation after transfection of a full-length p75NTR construct into these cells. They also show that p75NTR deficiency attenuates activation of the phosphatidylinositol 3-kinase → phospho-Akt/protein kinase B pathway in PC12 cells by oxidative stress or neurotrophic ligands and inhibition of Akt phosphorylation decreases the glutathione (GSH) content in PC12 cells. In addition, decreased de novo GSH synthesis and increased GSH consumption are observed in p75NTR-deficient cells. These findings indicate that p75NTR regulates cellular handling of ROS to effect a survival response to oxidative stress.
- Publication
Journal of Neurochemistry, 2009, Vol 110, Issue 1, p295
- ISSN
0022-3042
- Publication type
Academic Journal
- DOI
10.1111/j.1471-4159.2009.06137.x